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NIR-II Fluorescent Molecular Bottlebrush Prepared by Ring-Opening Polymerization for Programmed Cell Death Ligand‑1 Checkpoint Imaging
journal contribution
posted on 2021-11-03, 21:29 authored by Chao Wang, Pengfei Sun, Quli Fan, Wei HuangIn
the area of tumor therapy, the immune checkpoint drugs programmed
death-1 receptor (PD-1) and programmed death-ligand 1 (PD-L1) have
been widely used in clinical trials and shown excellent therapeutic
effects. The PD-L1 expression on cancer cells can be considered the
predictive biomarker for patients, and the second near-infrared (NIR-II)
window fluorescence imaging is ideal for immune checkpoint research.
Conjugated polymers, as a kind of organic semiconductor, have very
extensively applications in NIR-II fluorescence imaging, but the biological
application is limited with the poor water solubility. Here, we developed
a brush-on-brush molecular bottlebrush through a two-step “grafting
from” strategy by ring-opening polymerization (ROP). Then,
a PD-L1 monoclonal antibody (mAb) was conjugated with a molecular
bottlebrush to afford the fluorophore (anti-PD-L1)-P(TTQ-F)-g-(PLL30-g-(PGA)5) specific to the PD-L1 checkpoint. The fluorophore exhibits strong
NIR-II fluorescence signals and selective targeting ability of PD-L1.
Moreover, after an intravenous injection of (anti-PD-L1)-P(TTQ-F)-g-(PLL30-g-(PGA)5) into the BALB/c mice bearing CT26 tumors, the tumor-to-normal tissue
(T/NT) signal ratio sharply increased with a maximum T/NT = 11.90
at 12 h p.i. during the initial 12 h post-injection. This study provides
bright future outlooks for immune checkpoint imaging and further immunotherapy.
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window fluorescence imagingstep “ graftingselective targeting abilitypoor water solubility12 h pimmune checkpoint researchimmune checkpoint imagingii fluorescence signalsii fluorescence imagingl1 monoclonal antibodybrush molecular bottlebrushmolecular bottlebrushl1 checkpoint” strategywidely usedsecond nearrop ).programmed deathpredictive biomarkerorganic semiconductoropening polymerizationnormal tissuel1 expressiong f )-<extensively applicationsclinical trialscancer cellsbiological application>-( pll